Specific Aims: l) To elucidate the developmental decisions enacted by hematopoietic stem cells that lead to self-renewal, lineage commitment, and in lymphocytes, antigen receptor diversity. 2) To define cellular interactions and developmental decisions that occur during normal and neoplastic thymic lymphocyte maturation. 3) To study the role of cell surface homing receptors on normal lymphocyte homing and inflammation, and in malignant cell metastasis. 4) To study the events in mouse, pre-B leukemogenesis that results in abnormal proliferation and invasiveness; and to study the role of the 6C3/BPl metalloprotease in murine and human lymphoid neoplasms. 5) To continue to study a protochordate (Botryllus schlosseri) model for the evolution and function of allorecognition, including the genes that encode allorecognition behavior; and to develop genetic stocks and the laboratory mariculture techniques to make this unique invertebrate/vertebrate available to the scientific community.